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New Tool to Study Neurochemical Modulation of Feeding

研究进食神经化学调节的新工具

基本信息

批准号：
6827382
负责人：
SCOTT A SHIPPY
金额：
$ 12.77万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-12-01 至 2006-11-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): There is an increased prevalence of eating disorders and a growing appreciation of their health costs. In order to effect human health, a greater understanding of the mechanisms modulating ingestive behaviors is needed. The lateral hypothalamus has long been associated with feeding behavior and the neurotransmitter glutamate appears to play a unique, initiatory role at this region. In this proposal the low-flow push-pull perfusion method will be used to: 1.determine the precise location of an endogenous glutamatergic surge that is coincident with the initiation of a meal, 2.pharmacologically manipulate lateral hypothalamic sub areas to verify the link between ingestive behaviors and glutamate signaling. Because our new in vivo sampling method employs perfusion flow rates among the lowest of any in vivo sampling technique, the approximate 200-#m spatial resolution is significantly better than existing methods and no tissue damage is seen by light microscopy. Also, with low-flow push-pull sampling analyte recoveries are high and will be useful for recovery of large, slower diffusing molecules. We will determine optimal low-flow push-pull conditions for maximal protein recovery and the protein content will be determined for the most abundant cerebrospinal fluid proteins. Protease activity in perfusates will be measured and minimized by the use of capillary wall coatings. The developmental studies in this R21 proposal highlight the particular advantages that will be afforded by the use of the low-flow push-pull perfusion method and will lead to sampling conditions appropriate for future studies of neuropeptides implicated in feeding behavior. The unique capabilities of low-flow push-pull perfusion complement other sampling methodologies and are widely applicable to in vivo sampling studies.

描述（由申请人提供）：饮食失调的患病率越来越高，人们对其健康成本的认识也越来越高。为了影响人类健康，需要更深入地了解调节摄食行为的机制。外侧下丘脑长期以来一直与摄食行为和神经递质谷氨酸似乎在这一地区发挥独特的，启动作用。在本研究中，低流量推挽灌流法将用于：1.确定与进餐开始一致的内源性谷氨酸能峰的精确位置，2.连续操纵下丘脑外侧亚区以验证摄食行为和谷氨酸信号之间的联系。由于我们的新的体内采样方法采用的灌注流速在任何体内采样技术中最低，大约200 μ m的空间分辨率明显优于现有的方法，并且没有组织损伤被光学显微镜观察到。此外，低流量推挽采样分析物回收率高，将是有用的大，较慢的扩散分子的回收。我们将确定最佳的低流量推拉条件，以获得最大的蛋白质回收率，并确定最丰富的脑脊液蛋白质的蛋白质含量。将测量灌注液中的蛋白酶活性，并通过使用毛细血管壁涂层将其降至最低。本R21提案中的发育研究突出了使用低流量推拉灌注方法所具有的特殊优势，并将导致适合于未来研究摄食行为中涉及的神经肽的采样条件。低流量推拉灌注的独特功能补充了其他采样方法，并广泛适用于体内采样研究。